Selective Treatment With Magnetic Resonance Image Guided Pelvic Adaptive Radiation Therapy Combined With Total Neoadjuvant ChemoTherapy for the Conservative Management of Locally Advanced Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART
研究概览
简要总结
The purpose of this research study is to find out how safe and effective is treating patients with locally advanced rectal cancer (LARC) with chemotherapy first and then follow with radiation therapy to a higher dose than what is usually delivered and see if patients could have complete response and be spared from surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed, biopsy proven, rectal adenocarcinoma.
- •Primary tumor located ≤18 cm from margin verge.
- •Primary tumor either a T3N0 or T1-4 N positive (as defined per pelvic MRI; nodes ≤ 15 mm).
- •≥ 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Serum liver function tests values within the range of 1.5 x Upper Limit of Normal (within 6 weeks of enrollment).
- •Negative pregnancy test for women of child-bearing potential (within 4 weeks of enrollment).
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patient is assessed by a surgeon, medical oncologist and a radiation oncologist and deemed fit for Total Neoadjuvant ChemoTherapy (TNT) and surgery.
排除标准
- •Metastatic disease on initial work up (Chest and abdomen contrast enhanced CT scan).
- •Synchronous cancer found on colonoscopy.
- •Previous history of pelvic radiotherapy.
- •History of concurrent, active malignancy other than non-metastatic skin cancer within the last 2 years.
- •Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or uncontrolled severe cardiac arrhythmia, myocardial infarction within the last 6 months.
- •Psychiatric illness/social situations that would limit compliance with study requirements.
- •Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics or active tuberculosis (TB).
- •Patients with poorly controlled acquired immune deficiency syndrome (AIDS) who are not deemed candidates for FOLFOX, mFOLFIRINOX or CAPOX chemotherapy. Active connective tissue disorders, such as lupus or scleroderma, that, in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
- •Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
- •Sensory or motor neuropathy ≥ grade
- •Women who are breast feeding.
- •Exclusions due to MRI use in study: ferromagnetic metal in body/eye, pacemaker, defibrillator, other mechanical device, or extreme claustrophobia (medication with anti-anxiety agents, such as Ativan, may be attempted).
研究组 & 干预措施
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: Intensity-modulated radiation therapy (Radiation)
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: 5-fluorouracil (Drug)
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: Leucovorin (Drug)
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: Oxaliplatin (Drug)
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: Capecitabine (Drug)
SMART TNT Plan I
Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows:
Plan I (5 weeks):
-
MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks.
-
Concurrent chemotherapy beginning on Day 1 of RT either:
-
5-FU delivered 5 or 7 days per week.
-
Capecitabine (Xeloda) delivered 5 days per week.
After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.
干预措施: Irinotecan (Drug)
SMART TNT Plan II
Plan II boost RT (1 week): For participants not achieving cCR after chemo-radiation. Participants will receive MRI-guided accelerated radiation therapy (ART) boost to the primary tumor.
Participants achieving a cCR will continue to follow-up. Participants still showing residual tumor will undergo standard of care treatment including surgery and adjuvant chemotherapy per institutional guidelines during follow-up.
干预措施: Accelerated Radiation Therapy (Radiation)
结局指标
主要结局
Incidence of Toxicity Among Participants After Start Receiving MRI-g Pelvic ART
时间窗: Up to 30 months
Reported as the incidence of toxicity (adverse events and serious adverse events) in study participants after start of MRI-g Pelvic ART. Toxicity in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
次要结局
- Percentage of Real Negatives(Up to 6 months)
- Incidence of Acute and Long-Term Toxicity After Start of Study Therapy(Up to 30 months)
- Percentage of Participants with Documented Local Control(Up to 2 years)
- Percentage of Participants with Documented Distant Metastasis(Up to 2 years)
- Disease-free Survival (DFS) rate(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Health-related Quality of Life (HRQOL) Scores: Patient-Reported Outcomes Measurement Information System (PROMIS)(Up to 30 months)
- Health-related Quality of Life (HRQOL) Scores: Pittsburgh Sleep Quality Index (PSQI)(Up to 30 months)
研究者
Benjamin Spieler
Assistant Professor of Clinical
University of Miami